The prevalence of carbapenem-resistant Enterobacteriaceae has been increasing since the last ten years. This is a threat for an efficient antibiotherapy as carbapenems are the ultimate drugs for the treatment of Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) (now mainly CTX-M). In Belgium, more than 80% of the carbapenemases among the Enterobacteriaceae are OXA-48 (main species: Klebsiella pneumoniae). In many cases, OXA- 48-producing Enterobacteriaceae coproduce a CTX-M ESBL. They are also resistant to the cefalosporins and usually multiresistant to antibiotics (quinolones, co-trimoxazole, aminoglycosides, etc.). Temocillin has also become ineffective, and generally tigecycline and colistin still remain active against these bugs. Many questions about the carbapenemases remain unclear (e.g. The optimal therapeutic approach). It is worrisome that since 2012 many Escherichia coli with an OXA-48 carbapenemase are present in the commensal flora and in the urine of non-hospitalized patients.